Epithelial-stromal interactions play an essential role in normal growth, morphogenesis and cytodifferentiation in a variety of developing embryonic tissues. Available data indicate that such interactions play a significant role in adult tissues as well. There is some evidence to suggest that similar control mechanisms may also play a role in carcinogenesis. The present investigation is to test our working hypothesis which states that "although the primary target of urinary bladder carcinogen is the urothelial cells, the underlying mesenchymal stroma also undergoes primary but non-neoplastic alteration(s) which mediate(s) the neoplastic development in the overlying epithelium." The specific objectives are: 1. to determine whether or not carcinogen treatment induces specific stromal alterations in the urinary bladder with exert directive influences on the growth of normal and carcinogen-treated urothelium; 2. to determine whether or not carcinogen treatment produces angiogenesis factor(s) and, if it does, which structure is responsible for its production, epithelium or stroma, or both; 3. to determine whether or not stromal alterations are reversible; and finally 4. to determine whether or not the carcinogen-altered stroma affects the biological behavior of carcinoma cells. These studies will be conducted using 1) the heterotopically transplanted rat urinary bladder (HTB) denuded of its epithelium, 2) rat urothelial and stromal cells in culture, and 3) rat corneal bioassay for neovascularization.